ASXL1 and SETBP1 Mutations and Chronic Myelomonocytic Leukemia

Ayalew Tefferi, M.D.

Chronic myelomonocytic leukemia (CMML) is a clonal, hematopoietic stem cell disorder, with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms. The World Health Organization (WHO) diagnostic criteria for CMML includes analysis of various gene mutations, including ASXL1 and SETBP1.

Mayo Clinic researchers, first author Ayalew Tefferi, M.D., in collaboration with the French consortium for CMML, conducted a study published in Leukemia to clarify the prognostic relevance of ASXL1 and SETBP1 mutations, among others, in World Health Organization-defined CMML and its added value to the Mayo prognostic model.

Past studies have demonstrated a negative prognostic impact for ASXL1 mutations in patients with CMML. A previous Mayo Clinic study analyzed several clinical and laboratory parameters, including ASXL1 mutations, in patients with CMML. In this study, ASXL1 mutations were detected in 49 percent of patients and did not affect either overall or leukemia-free survival. The study resulted in the development of the Mayo prognostic model, with three risk categories, low (0 risk factor), intermediate (1 risk factor) and high (≥2 risk factors), with median survivals of 32, 18.5 and 10 months, respectively.

Additionally, SETBP1 mutations were seen in 12 of 195 French patients with CMML and were reported to affect both overall and leukemia-free survival. Similar observations were made by a Mayo Clinic study where SETBP1 mutations were seen in 8 of 179 patients with CMML

In the current study, 466 patients underwent bone marrow examination and cytogenetic evaluation at diagnosis. Based on the study results, neither ASXL1 nor SETBP1 mutations predicted leukemic transformation. The study confirms the independent prognostic value of nonsense/frameshift ASXL1 mutations in CMML and signifies its added value to the Mayo prognostic model, as had been shown previously in the French consortium model.

Read the full article for more information.

Additional Mayo Clinic authors include: Mrinal Patnaik, M.B.B.S, Curtis Hanson, M.D., Terra Lasho, Ph.D., Rhett Ketterling, M.D., Christy Finke, Ryan Knudson


Kelley Schreiber

Kelley Schreiber is a Marketing Channel Manager at Mayo Medical Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her new kitten, and exploring new foods.


I AM 51 female that underwent a bone marrow biopsy in october 2014 due to anemia. The results: Mildly hypocellular marrow for age with progressive hematopoiesis And mutations of uncertain significance detected in the ETV6 And SETBP1 genes. In the Megakayopoiesis: Megakaryocytes appear adequate in a patchy distribution And show mostly un remarkable morphlolgy, but occasional hypolobated forms are Present. I live in the island of Puerto Rico And There is no Geneticist here for adults that could see me And tell me what this means. I will apppreciate your advice. Thank you.

Someone will be contacting directly on this subject.

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